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Spontaneous gene mutations may account for half of all cases of autism in males: By now you’ve probably heard about this finding, and about a new model of autism genetics published in Proceedings of the National Academy of Sciences. For a cogent overview, see John Timmer’s July 24th post on Ars Technica. The title of the post, Autism may all be in the genes contains a hidden polemic: Most people take the view that a person has a “genetic predisposition to autism which is “triggered by environmental factors” and shy away from saying that autism is wholly genetic.
Timmer notes that
“genetics can accurately model much of the incidence of autism if you make some very specific assumptions about modes of inheritance”—assumptions which are based on “suggested by what’s already known about the disease.”
More specifically:
Under geneticist Michael Wigler of Cold Spring Harbor Laboratory in Long Island, NY, researchers studied families who have two or more autistic children and considered what the chances were for families whose first two children were autistic to have a third autistic child. In 86 families with two autistic children and with a third, male child, 42 of the third-born children had autistic symptoms. Notes the July 24th Nature.com:
This suggests that parents had a one-in-two chance of passing on a mutation to their offspring, matching a dominant inheritance pattern……
Using mathematical models, Wigler’s team found that the simplest way to describe the patterns of autism inheritance was to divide parents into two risk classes: those who carry a pre-existing autism-causing mutation, and those who do not.
The models suggest that about half of autistic children are born to parents with no previous genetic predisposition to autism, suggesting that the cases are caused by spontaneous mutations.
According to Wigler and his research team, mothers spontaneously acquire genetic mutations that are specific for autism. While the mothers themselves do not have autism, there is a 50% chance that they will transit the autism-related mutations to their children. There are, therefore, families who are at a “low risk” to have an autistic child, and families who are “high risk” (in which the mother carries the mutations but does not show autistic symptoms).
The July 24th Scientific American also brings up the notion of families who are at a “high risk” of having an autistic child in New Theory about Autism’s Roots:
The team determined that most cases of autism arise from novel, spontaneous mutations passed down from one or both parents, resulting in large gaps in a person’s genome often encompassing several genes, which are then disrupted or inactivated. (This loss of genetic code—known as copy number variation—results in an offspring receiving only one of the standard two copies of a gene, which could cause an insufficient amount of protein to be produced by those genes.) In most instances, this mutation will result in an autistic child. However, in some cases—more likely in girls than boys—the recipient of this mutation will not produce any symptoms.
“When that child matures and becomes a parent, they have a 50 percent chance of transmitting … [their mutation] … to a child that might not be as lucky as they were, especially if … [its] … a boy,” Wigler says. “So, they will be transmitting this with close to a 50 percent frequency—and that is the source of the high-risk families.”
Some might respond to these findings by saying that mercury or some environmental toxin created the genetic mutations. My response—my very personal, autism-mother-on-her-soapbox response—is to ask: Ok, spontaneous genetic mutations——–so, are we—-am I—-in the “high risk” 50%?
I am going to posit that I am. As I review my extended family, many members of which are engineers or work in computers or write software or are in IT—some members of which could be placed on some spectrum of quirky geekitude0000I find it perhaps notable that I (who have always written and loved poetry, and don’t do math), have an autistic child (and very happily so, after yet another afternoon passed at the swimming pool praising Charlie for not minding too much that the water slide was closed, an ABA session during which he kept running straightways out the garage door and struggled to say the /ch/ in his own name, and trying to show him how to push the shopping cart s-l-o-w-l-y and not into other shoppers). Some have suggested that there is a sort of “autism cluster” in Silicon Valley; the Valley is where many of my cousins live and work, while here I have been away on the East Coast teaching Latin and Greek and the Classics and teaching college students how to write a good essay.
Maybe those autism genes skipped around and settled in me, who find more and more of Charlie in me and of me in Charlie with each passing day.
Mutatis mutandis goes the Latin: That which has been changed, had to be changed. There can be no doubt that my life has been profoundly changed and shaped by the experience of raising Charlie—-the change of a lifetime that I am grateful for. But what new and difficult choices might parents face if they are told that they are at “high risk” to have a child like him? What changes might happen in our world and among us human beings?
Hi,
Please consider visiting http://www.neoteny.org/?cat=7 to review a unique and unorthodox theory for the cause of autism.
Thank you,
Andrew Lehman
1510 days ago
[...] as noted in PsychPort.com. Many of the DNA variants found in the study are, like those in an autism study under Michael Wigler, another Cold Spring geneticist, occur [...]
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[...] that of researchers using classical Mendelian genetics; last year he published two articles about spontaneous mutation and autism. A March 2007 paper in Science suggested that large genetic events—”copy number [...]
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Caroline L—-the word autism definitely seems to have been overly endowed with many and multiple meaning!
I hope we can all find some common ground, despite this.
best wishes—
Eye on DNA has a recent post on Environment, Epigenetics, and DNA.
Epigenetics a bit off topic. I saw this
http://www.pbs.org/wgbh/nova/sciencenow/
It talks about it. If there is truth to this then genes can turned on or off. While this does no the gluten free diet is proved. It does raise interesting possibilities about amelioration of the least desirable charateristics.
Joe Mele accurately states that autism might be polygenic, the interactions of more than one gene that ’cause’ autism. Excluding genetic mental retardation syndromes (Tuberous Sclerosis, Fragile X) there is still not one autism specific gene that has been found. The polygenic theory remains unproven. Michael Rutter, perhaps the leading authority on autism and the child psychiatrist who originally developed the concept of the broad autism phenotype seems to opening up the door to gene-environment interactions as likely involved in at least part of autism etiology. A few years ago he actually referred to the scientists who deeply believe that autism is a genetic only condition as ‘genetic evangelists’.
Okay, so there is no confusion I will go by “Caroline L.” from now on. I often comment on Kristina’s beautifully written and informative posts.
It is the first time and only place I have ever commented on the issues that concern me most:
* all persons regardless of health conditions or differing abilities deserve respect and the non-patronising supports each individual requires. If for nothing else, then for good karma, because in the blink of an eye, we all could lose the ability to communicate and function independently.(dementia, stroke, accident, etc.)
SO, back to this post on CSHL, it does not matter to me about the possibility of a prenatal test. I would like to see more scientific research on this whole ‘regressive autism’ label because I do not think it is autism at all. The people who comment on AutismVox who can describe from personal experience what autism is describe something very different from what I have seen in the so – called ‘regressive autism’ subset.
* I believe autism spectrum disorders are being over-diagnosed. For those individuals and parents who feel it fits, and the services and therapies are appropriate, that is great. But some education professionals make snap judgements based on a child’s behavior at one point in time and the child can be trapped in a cycle of wildly inappropriate placements.
*I believe in properly supported inclusion. I do not believe in mandatory segregation.
*I believe in appropriate individualized education plans and transition plans for each individual – not just photocopying some random goals that fit the ‘diagnosis’.
* I believe in teachers and other education staff treating children in their care with respect and empathy, and working on the assumption that the child/adult understands everything, even if ‘non-verbal’.
To Caroline 2,
I can understand your despair for your child. Excellent behavior modification therapy delivered in a natural, loving, relaxed, empathetic way can perform miracles. PassionlessDrone makes a great suggestion as well – we have had great success (knock wood) from probiotics.
with best wishes, Caroline L.
(apologies for length)
Hello friends –
Just the other night I saw an episode of Nova Science Now that went over epigenitics; the interaction of genetics and environment.
It was completely fascinating and I am willing to recommend it.
Nova Now Link
There is a three or four minute flash moive, ‘A tale of two mice’ that has shows the result of some interesting studies of genetically identical mice that look nothing alike.
Check it out!
-pD
Caroline –
“My child spends a large proportion of the day self-mutilating and as far as we can judge because he is non-verbal and has virtually has no other communication, he is miserable and his life is not worth living.”
Watching my son hurt himself was easily the most difficult part of his regression into autism.
My son stopped head banging completely within two months of starting anti fungal treatments and introduction of friendly bacteria to his gut. If you have not investigated biomedical treatments, I urge you to do so. Likewise, others have reported success using behavior modification training.
Stay strong.
-pD
Note to readers: 2 different commenters have posted as “Caroline” in this thread.
Caroline: What kinds of efforts have been made to help to teach your son other things to do besides the self-mutilating, if I may ask? My son used to head-bang regularly and on anything.
If research can be funded to determine the genetic (and therefore prenatal screening test) difference between high functioning or savant autistics and people with autistic disorder then maybe science might be able to enable society to keep their genius in the human gene pool. however what i think is more to the point is the quality of life of the person with autism. My child spends a large proportion of the day self-mutilating and as far as we can judge because he is non-verbal and has virtually has no other communication, he is miserable and his life is not worth living. I hope he dies young for his sake but also for the sake of his siblings whom I know love him so much they feel the same way too. we hate to see him suffer. He is on medication but to no avail. At least Einsttein and Mozart may have been able to say if they were unhappy or in pain or sitting in their own faeces.may be society ise being selfish to want a genius at the expense of a child doomed to a lifetime of suffering?????????? I would have had an abortion at the drop of a hate to prevent the pain my child is going through now and I hope my other kids choose to adopt or have a surrogate.
To add to Joe’s thoughts about “no single gene,” I’d like to share G.C. Williams definition of the term “gene” (from Adaptation and Natural Selection):
“I use the term gene to mean ‘that which segregates and recombines with appreciable frequency.’ … A gene could be defined as any hereditary information for which there is a favorable or unfavorable selection bias equal to several or many times its rate of endogenous change.”
I had a chance to read the paper and have a couple of thoughts:
In the discussion part of the paper, the authors state: “We must emphasize at the outset that our biological interpretation of the risk models assumes that risk is determined by genetic factors, and thus, except for their appealing simplicity, the risk models themselves should not be taken as evidence for genetic causation.”
In other words (my other words, anyway) – “We don’t know if autism is purely genetic in nature, but if it is we think this could explain how that works.”
The authors do offer an explanation of why boys are more affected than girls: “To explain greater penetrance in males, we need merely consider the hypothesis that autism involves loss of cognitive abilities related to social skills, language, and repetitive behavior that may already be targets of sexual dimorphism and hence these traits are already sensitive to perturbation.”
Treading on dangerous ground, especially if you bring this up to those who would like to believe the tabula rasa theory of the mind, that everyone – boys and girls alike – start off equal.
The paper does not mention any incidences of autistic men fathering children, or the impact that has on prevalence in children. I know it’s not because those cases don’t exist. Perhaps it is just statistically insignificant?
While I’m intrigued by the arguments about autism being underpinned by a genetic mutation, I still wonder about the wide variety of ways autism appears to manifest itself — in some cases from birth, in others as a “regression” and a loss (or at least substantial modification) of skills. How would a single genetic configuration (rather than genetic-predisposition-plus-life/external-factors) account for this? (As you all can tell, I’m not a scientist… :-)
Always glad to endorse you, Joe—-I do think that it is too simple to say that there is an “autism gene,” that there is a single gene for autism.
The root word of “mutation,” the Latin mutare, simply means to change without any of the pejorative associations in such English words as “mutant” or “mutation.” I wonder if those pejorative associations are in people’s minds in talking about genetic mutations.
RAJ is not quite right despite Dr chew’s endorsement. Nobody said there are not seen elsewhere. I made the point that a study said there is a greater number of mutations in the ASD population.
Also this notion of no single gene is misleading. Autism can be an effect of a set of genes without being “due to a gene”. So in fact no single gene doesnt make it not genetic. Autism can be in the various flavors due to more than one set of genes that can overlap.